ITMI20100375A1 - COMPOSITION INCLUDING PROBIOTIC BACTERIA FOR THE TREATMENT OF PATHOLOGIES ASSOCIATED WITH THE ALTERATION OF THE IMMUNE SYSTEM. - Google Patents

COMPOSITION INCLUDING PROBIOTIC BACTERIA FOR THE TREATMENT OF PATHOLOGIES ASSOCIATED WITH THE ALTERATION OF THE IMMUNE SYSTEM. Download PDF

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ITMI20100375A1
ITMI20100375A1 IT000375A ITMI20100375A ITMI20100375A1 IT MI20100375 A1 ITMI20100375 A1 IT MI20100375A1 IT 000375 A IT000375 A IT 000375A IT MI20100375 A ITMI20100375 A IT MI20100375A IT MI20100375 A1 ITMI20100375 A1 IT MI20100375A1
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dsm
composition
filed
lactobacillus
use according
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IT000375A
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Italian (it)
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Giovanni Mogna
Luca Mogna
Gian Paolo Strozzi
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Probiotical Spa
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Priority to ITMI2010A000375A priority Critical patent/IT1398553B1/en
Application filed by Probiotical Spa filed Critical Probiotical Spa
Priority to EP11717732.9A priority patent/EP2544698B1/en
Priority to DK13166218.1T priority patent/DK2626076T3/en
Priority to PL13166218T priority patent/PL2626076T3/en
Priority to HUE13166218A priority patent/HUE030888T2/en
Priority to PCT/IB2011/000490 priority patent/WO2011110918A1/en
Priority to DK11717732.9T priority patent/DK2544698T3/en
Priority to EP13166218.1A priority patent/EP2626076B1/en
Priority to CN201510082517.4A priority patent/CN104800247A/en
Priority to RU2012140052/15A priority patent/RU2605293C2/en
Priority to HUE11717732A priority patent/HUE029245T2/en
Priority to PT131662181T priority patent/PT2626076T/en
Priority to US13/583,477 priority patent/US8734783B2/en
Priority to RU2016129186A priority patent/RU2712751C9/en
Priority to AU2011225798A priority patent/AU2011225798B2/en
Priority to BR112012022755-6A priority patent/BR112012022755B1/en
Priority to PT117177329T priority patent/PT2544698T/en
Priority to ES13166218.1T priority patent/ES2603629T3/en
Priority to KR1020127026327A priority patent/KR101872946B1/en
Priority to PL11717732T priority patent/PL2544698T3/en
Priority to ES11717732.9T priority patent/ES2581803T3/en
Priority to CN201180019385.0A priority patent/CN103037876B/en
Priority to CA2792343A priority patent/CA2792343C/en
Priority to JP2012556603A priority patent/JP5931754B2/en
Priority to UAA201211024A priority patent/UA111715C2/en
Publication of ITMI20100375A1 publication Critical patent/ITMI20100375A1/en
Priority to ZA2012/07377A priority patent/ZA201207377B/en
Publication of IT1398553B1 publication Critical patent/IT1398553B1/en
Application granted granted Critical
Priority to US14/286,308 priority patent/US9498503B2/en
Priority to ZA2014/09369A priority patent/ZA201409369B/en
Priority to JP2016029244A priority patent/JP6182628B2/en
Priority to US15/294,464 priority patent/US9931363B2/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/66—Microorganisms or materials therefrom
    • A61K35/74—Bacteria
    • A61K35/741—Probiotics
    • A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
    • A61K35/745—Bifidobacteria
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/02—Nasal agents, e.g. decongestants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2200/00—Function of food ingredients
    • A23V2200/30—Foods, ingredients or supplements having a functional effect on health
    • A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
    • A23V2200/3204—Probiotics, living bacteria to be ingested for action in the digestive tract
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2400/00—Lactic or propionic acid bacteria
    • A23V2400/11—Lactobacillus
    • A23V2400/181—Salivarius
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K2035/11—Medicinal preparations comprising living procariotic cells
    • A61K2035/115—Probiotics

Description

DESCRIZIONE dell'invenzione avente per titolo: "Composizione comprendente batteri probiotici per il trattamento di patologie associate con le alterazioni del sistema immunitario" . DESCRIPTION of the invention entitled: "Composition comprising probiotic bacteria for the treatment of pathologies associated with alterations of the immune system".

La presente invenzione si riferisce a una composizione comprendente batteri probiotici per il trattamento di patologie associate con le alterazioni del sistema immunitario. In particolare, la presente invenzione si riferisce all'uso di selezionati batteri probiotici per la preparazione di una composizione per il trattamento di allergie, come la dermatite atopica. The present invention relates to a composition comprising probiotic bacteria for the treatment of pathologies associated with alterations of the immune system. In particular, the present invention relates to the use of selected probiotic bacteria for the preparation of a composition for the treatment of allergies, such as atopic dermatitis.

E' noto che la Dermatite Atopica (nel prosieguo DA per brevità) à ̈ un disordine cutaneo di tipo cronico con riacutizzazioni che inizia nel periodo neonatale o nell'infanzia e che può perdurare nell'età adulta. Pertanto le fasi della DA si dividono in neonatale, infantile e dell'adulto. La DA à ̈ una malattia infiammatoria della cute che, come l'asma e la rinite allergica, à ̈ associata all'infiltrazione locale di linfociti T che producono interleuchina 4 (IL-4) ed interleuchina-5 (IL-5). It is known that Atopic Dermatitis (hereinafter DA for brevity) is a chronic skin disorder with exacerbations that begins in the neonatal period or in childhood and which can persist into adulthood. Therefore the stages of AD are divided into neonatal, infantile and adult. AD is an inflammatory skin disease which, like asthma and allergic rhinitis, is associated with the local infiltration of T lymphocytes that produce interleukin 4 (IL-4) and interleukin-5 (IL-5).

L'IL-4, come à ̈ noto, regola lo sviluppo del fenotipo T helper 2 (Th2) con conseguente iperproduzione di immunoglobuline (Ig) E ed eosinofilia. Elevati livelli di Ig E a livello del siero e skin tests positivi per allergeni alimentari e inalanti possono essere dimostrati nell'80-90% dei soggetti con dermatite atopica. IL-4, as it is known, regulates the development of the T helper 2 (Th2) phenotype with consequent overproduction of immunoglobulin (Ig) E and eosinophilia. Elevated serum Ig E levels and positive skin tests for food allergens and inhalants can be demonstrated in 80-90% of subjects with atopic dermatitis.

La DA si basa sia su fattori genetici che su fattori immunologici , anche se un gran numero di fattori esterni può modificare la sua espressione. Nel 60% dei casi di DA si può dimostrare una storia familiare per atopia, in altre parole se un genitore ha una diatesi atopica vi sono il 60% delle possibilità che i figli siano atopici. AD is based on both genetic and immunological factors, although a large number of external factors can modify its expression. In 60% of cases of AD, a family history of atopy can be demonstrated, in other words if a parent has atopic diathesis there is a 60% chance that the children are atopic.

L 'atopia e' la predisposizione genetica a sviluppare reazioni anafilattiche localizzate in seguito a contatto, ingestione, inoculazione o inalazione di allergeni. Atopy is the genetic predisposition to develop localized anaphylactic reactions following contact, ingestion, inoculation or inhalation of allergens.

I fattori immunologici presi in considerazione nell'eziologia della DA sono: l'allergia agli alimenti, l'allergia indotta da allergeni e irritanti da contatto, l'allergia indotta da aeroallergeni e le anomalie dell'immunoregolazione. The immunological factors considered in the etiology of AD are: food allergy, allergy induced by allergens and contact irritants, allergy induced by aeroallergens and immunoregulatory abnormalities.

Nel panorama dei trattamenti diretti verso la cura e/o prevenzione delle allergie e, in particolare, verso il trattamento della dermatite atopica spiccano molte cure a base di farmaci. In the panorama of treatments directed towards the cure and / or prevention of allergies and, in particular, towards the treatment of atopic dermatitis, many drug-based treatments stand out.

Tuttavia, non esiste una cura, avente efficacia assoluta, ma si può far capo a determinate precauzioni contro l'insorgenza delle allergie o, al bisogno, a rimedi per mitigare i fastidiosi sintomi, come il prurito. However, there is no cure, with absolute efficacy, but certain precautions against the onset of allergies or, if necessary, remedies to mitigate the annoying symptoms, such as itching, can be used.

E noto che selezionati ceppi di batteri probiotici sono in grado di interegire con il sistema immunitario. Questa interazione e' in grado di modificare il tipo e il grado di protezione contro i patogeni. Selected strains of probiotic bacteria are known to interact with the immune system. This interaction is able to modify the type and degree of protection against pathogens.

Inoltre, l'alterazione dell'omeostasi della flora intestinale miocrobica (ingerita e residente) Ã ̈ alla base di alcune teorie secondo le quali l'interazione microbi/ospite ha un effetto sulle malattie atopiche. Furthermore, the alteration of the homeostasis of the myocrobial intestinal flora (ingested and resident) is the basis of some theories according to which the microbial / host interaction has an effect on atopic diseases.

La Richiedente si à ̈ prefissata lo scopo di valutare gli effetti di una terapia a base di batteri probiotici sul decorso clinico e sulla qualità della vita di pazienti con DA moderata o severa. The Applicant has set itself the aim of evaluating the effects of a therapy based on probiotic bacteria on the clinical course and on the quality of life of patients with moderate or severe AD.

La diagnosi di DA moderata/severa à ̈ stata valutata mediante l'utilizzo di un indice standardizzato di severità della DA (SCORAD index = SCORing Atopic Dermatitis). Tale indice à ̈ noto agli esperti del settore. The diagnosis of moderate / severe AD was assessed using a standardized index of AD severity (SCORAD index = SCORing Atopic Dermatitis). This index is known to experts in the field.

E' stato trovato che specifici batteri probiotici hanno un elevato effetto ìmmunomodulatore e sono perciò utili per il trattamento di patologie associate con le alterazioni del sistema immunitario. It has been found that specific probiotic bacteria have a high immunomodulatory effect and are therefore useful for the treatment of diseases associated with alterations in the immune system.

Forma oggetto della presente invenzione una composizione comprendente almeno una coltura di batteri probiotici, come rivendicato nell'unita rivendicazione indipendente. The object of the present invention is a composition comprising at least one culture of probiotic bacteria, as claimed in the appended independent claim.

Inoltre, forma oggetto della presente invenzione l'uso di almeno una coltura di batteri probiotici, come rivendicato nell'unita rivendicazione indipendente. Furthermore, the object of the present invention is the use of at least one probiotic bacteria culture, as claimed in the appended independent claim.

Altre forme preferite della presente invenzione sono riportate, nella descrizione dettagliata che segue, a titolo esemplificativo e, pertanto, non limitativo della portata della presente invenzione. Other preferred forms of the present invention are reported, in the detailed description which follows, by way of example and, therefore, not limiting the scope of the present invention.

La Richiendente ha selezionato le seguenti colture di batteri probiotici : Richiendente has selected the following probiotic bacteria cultures:

1) Lactobacillus salivarius (LS01) DSM 22775, depositata il 23.07.2009, dalla Società Probiotical SpA di Novara -Italia; 1) Lactobacillus salivarius (LS01) DSM 22775, filed on 23.07.2009, by the Società Probiotical SpA of Novara - Italy;

2) Bifidobacterium breve (BR03) DSM 16604, depositata il 20.07.2004, dalla Società Probiotical SpA di Novara -Italia; 2) Bifidobacterium brevis (BR03) DSM 16604, filed on July 20, 2004, by the Società Probiotical SpA of Novara - Italy;

3) Lactobacillus pentosus (LPS01) DSM 21980, depositata il 14.11.2008, dalla Società Probiotical SpA di Novara -Italia; 3) Lactobacillus pentosus (LPS01) DSM 21980, filed on November 14, 2008, by the Società Probiotical SpA of Novara - Italy;

4) Streptococcus thermophilus (FP4) DSM 18616, depositata il 13.09.2006, dalla Società Mofin Srl di Novara -Italia; 4) Streptococcus thermophilus (FP4) DSM 18616, filed on 13.09.2006, by the Mofin Srl company of Novara - Italy;

5) Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605, depositata il 20.07.2004, dalla Società Probiotical SpA di Novara - Italia; e 5) Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605, filed on 20.07.2004, by the Società Probiotical SpA of Novara - Italy; And

6) Lactobacillus acidophilus (LA02) DSM 21717, depositata il 06.08.2008, dalla Società Probiotical SpA di Novara -Italia. 6) Lactobacillus acidophilus (LA02) DSM 21717, filed on 06.08.2008, by the Società Probiotical SpA of Novara - Italy.

Le sopra riportate colture sono state tutte depositate presso il Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, (DSMZ) in Germania, in accordo con il Trattato di Budapest . The above cultures were all deposited with the Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, (DSMZ) in Germany, in accordance with the Budapest Treaty.

Nel contesto della presente invenzione, le colture di batteri probiotici sopra riportate possono essere sottoforma di batteri vivi, batteri morti o loro componenti cellulari, estratti cellulari o lisati. In the context of the present invention, the probiotic bacteria cultures described above can be in the form of live bacteria, dead bacteria or their cellular components, cell extracts or lysates.

In una realizzazione preferita, la composizione comprende almeno una coltura di batteri per uso come composizione immunomodulante in grado di modulare il sistema immunitario. In a preferred embodiment, the composition comprises at least one culture of bacteria for use as an immunomodulating composition capable of modulating the immune system.

L'espressione "composizione immunomodulante" significa che la composizione à ̈ in grado di modulare il sistema immunitario nel senso che à ̈ in grado di stimolare/indurre alcune risposte del sistema immunitario rendendolo più reattivo, intervenendo per esempio, attraverso la produzione di specifiche citochine . The expression "immunomodulating composition" means that the composition is able to modulate the immune system in the sense that it is able to stimulate / induce some responses of the immune system making it more reactive, intervening for example, through the production of specific cytokines .

Vantaggiosamente, detta composizione immunomodulante induce il sistema immunitario verso una produzione di citochine di tipo 1. Advantageously, said immunomodulating composition induces the immune system towards a production of type 1 cytokines.

Pertanto, detta composizione immunomodulante e' in grado di curare e/o prevenire le patologie associate con le alterazioni del sistema immunitario quali allergie e immunodeficenze . Therefore, said immunomodulating composition is able to cure and / or prevent the pathologies associated with the alterations of the immune system such as allergies and immunodeficiencies.

In accordo ad una delle sue realizzazioni, la presente invenzione concerne una composizione comprendente almeno una coltura di batteri probiotici scelta tra la coltura di Lactobacillus salivarìus (LS01) DSM 22775, Bìfidobacterium breve (BR03) DSM 16604 e Lactobacillus pentosus (LPS01) DSM 21980. According to one of its embodiments, the present invention relates to a composition comprising at least one culture of probiotic bacteria chosen from the culture of Lactobacillus salivarìus (LS01) DSM 22775, Bìfidobacterium breve (BR03) DSM 16604 and Lactobacillus pentosus (LPS01 ) DSM 21980.

In una realizzazione preferita, la composizione comprende detta coltura di Lactobacillus salivarìus (LS01) DSM 22775 e detta coltura di Bifidobacterium breve (BR03) DSM 16604 in associazione con almeno un'altra coltura scelta dal gruppo comprendente: Lactobacillus pentosus (LPS01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 e Lactobacillus acidophilus (LA02) DSM 21717. In a preferred embodiment, the composition comprises said culture of Lactobacillus salivarìus (LS01) DSM 22775 and said culture of Bifidobacterium breve (BR03) DSM 16604 in association with at least one other culture chosen from the group comprising: Lactobacillus pentosus (LPS01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 and Lactobacillus acidophilus (LA02) DSM 21717.

In accordo a un'altra delle sue realizzazioni preferite, la presente invenzione concerne l'uso di almeno una coltura di batteri probiotici scelta tra la coltura di Lactobacillus salivarìus (LS01) DSM 22775, Bifidobacterium breve (BR03) DSM 16604 e Lactobacillus pentosus (LPS01) DSM 21980, per la preparazione di una composizione per il trattamento preventivo e/o curativo della dermatite atopica. According to another of its preferred embodiments, the present invention concerns the use of at least one culture of probiotic bacteria chosen from the culture of Lactobacillus salivarìus (LS01) DSM 22775, Bifidobacterium breve (BR03) DSM 16604 and Lactobacillus pentosus (LPS01) DSM 21980, for the preparation of a composition for the preventive and / or curative treatment of atopic dermatitis.

Preferibilmente, l'invenzione concerne l'uso di detta coltura di Lactobacillus salivarius (LS01) DSM 22775 e detta coltura di Bifidobacterium breve (BR03) DSM 16604 in associazione con almeno un'altra coltura scelta dal gruppo comprendente: Preferably, the invention relates to the use of said culture of Lactobacillus salivarius (LS01) DSM 22775 and said culture of Bifidobacterium breve (BR03) DSM 16604 in association with at least one other culture selected from the group comprising:

Lactobacillus pentosus (LPS01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 e Lactobacillus acidophilus (LA02) DSM 21717, per la preparazione di una composizione per il trattamento preventivo e/o curativo della dermatite atopica. Lactobacillus pentosus (LPS01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 and Lactobacillus acidophilus (LA02) DSM 21717, for the preparation of a composition for the preventive and / or curative treatment of atopic dermatitis.

Vantaggiosamente, la composizione à ̈ costituita da Lactobacillus salivarius (LS01) DSM 22775 e di Bifidobacterium breve (BR03) DSM 16604 in un rapporto in peso compreso da 1:3 a 3:1, preferibilmente 1:1. Advantageously, the composition consists of Lactobacillus salivarius (LS01) DSM 22775 and of Bifidobacterium breve (BR03) DSM 16604 in a weight ratio ranging from 1: 3 to 3: 1, preferably 1: 1.

Alternativamente, la composizione à ̈ costituita da Lactobacillus salivarius (LS01) DSM 22775, Bifidobacterium breve (BR03) DSM 16604 e L. pentosus (LPS01) DSM 21980, preferibilmente in un rapporto in peso 1:1:1. Alternatively, the composition consists of Lactobacillus salivarius (LS01) DSM 22775, Bifidobacterium brew (BR03) DSM 16604 and L. pentosus (LPS01) DSM 21980, preferably in a 1: 1: 1 weight ratio.

Le colture batteriche oggetto della presente invenzione possono essere considerate come "ingredienti attivi" che possono essere mescolate, nelle dovute proporzioni, con eccipienti fisiologicamente e/o farmaceuticamente accettabili. The bacterial cultures object of the present invention can be considered as "active ingredients" which can be mixed, in the due proportions, with physiologically and / or pharmaceutically acceptable excipients.

Per migliorare la loro attività, gli ingredienti attivi possono essere somministrati per via sistemica, vantaggiosamente per via orale, sottoforma di composizioni allo stato solido, preparate secondo le tecniche note all'esperto del settore. To improve their activity, the active ingredients can be administered systemically, advantageously orally, in the form of solid state compositions, prepared according to the techniques known to those skilled in the art.

In una realizzazione preferita, le composizioni sono in forma di liofilizzato, polveri, granuli, compresse, capsule softgel o sospensioni. In a preferred embodiment, the compositions are in the form of lyophilisate, powders, granules, tablets, softgel capsules or suspensions.

Le composizioni della presente invenzione possono essere composizioni farmaceutiche, dietetiche, alimentari o nutraceutiche . The compositions of the present invention can be pharmaceutical, dietary, food or nutraceutical compositions.

Le composizioni della presente invenzione possono inoltre comprendere fibre alimentari ad attività prebiotica quali frutto-oligosaccaridi (FOS), inulina, gomma di guar parzialmente idrolizzata (PHGG). The compositions of the present invention can further comprise dietary fibers with prebiotic activity such as fructo-oligosaccharides (FOS), inulin, partially hydrolyzed guar gum (PHGG).

Le composizioni farmaceutiche, dietetiche, alimentari o nutraceutiche della presente invenzione comprendono almeno una coltura di batteri probiotici, come sopra indicate. La concentrazione finale della composizione à ̈ compresa da lxl0^ a 1x10<11>UFC/g di composizione, preferibilmente da lxl0^ a 1x10<10>UFC/g di composizione. The pharmaceutical, dietary, food or nutraceutical compositions of the present invention comprise at least one culture of probiotic bacteria, as indicated above. The final concentration of the composition ranges from 1x10 ^ to 1x10 <11> UFC / g of composition, preferably from 1x10 ^ to 1x10 <10> UFC / g of composition.

Le composizioni della presente invenzione, che comprendono selezionati batteri probiotici, sono utili come composizioni immunomodulanti in grado di modulare il sistema immunitario. The compositions of the present invention, which include selected probiotic bacteria, are useful as immunomodulating compositions capable of modulating the immune system.

Dette composizioni sono in grado di curare e/o prevenire le patologie associate con le alterazioni delle funzioni delle seguenti citochine: Thl (IFN-γ e IL-12) e Th2 (IL-4, IL-5 e IL-10) . Said compositions are able to cure and / or prevent the pathologies associated with the alterations of the functions of the following cytokines: Thl (IFN-γ and IL-12) and Th2 (IL-4, IL-5 and IL-10).

Inoltre, dette composizioni sono in grado di indurre il sistema immunitario inducendo quest'ultimo verso una produzione di citochine di tipo 1. Furthermore, said compositions are able to induce the immune system by inducing the latter towards a production of type 1 cytokines.

Pertanto, le composizioni della presente invenzione trovano valida applicazione per il trattamento preventivo e/o curativo di allergie e stati di immunodeficienza. Therefore, the compositions of the present invention find valid application for the preventive and / or curative treatment of allergies and immunodeficiency states.

Vantaggiosamente, le composizioni della presente invenzione trovano valida applicazione nel trattamento preventivo e/o curativo della dermatite atopica. Advantageously, the compositions of the present invention find valid application in the preventive and / or curative treatment of atopic dermatitis.

Vantaggiosamente, l'assunzione da parte dei pazienti affetti da dermatite atopica DA di una composizione probiotica comprendente la coltura di Lactobacillus salivarius (LS01) DSM 22775 e la coltura di Bifidobacterium breve (BR03) DSM 16604, ad una concentrazione compresa da lxl0^ a 1x10 UFC, preferibilmente 1x10^ UFC/g, determina una diminuzione dell'indice di Scorad (un valore di Scorad inferiore indica una qualità' della vita migliore). Advantageously, the assumption by AD atopic dermatitis patients of a probiotic composition comprising the culture of Lactobacillus salivarius (LS01) DSM 22775 and the culture of Bifidobacterium breve (BR03) DSM 16604, at a concentration ranging from lxl0 ^ to 1x10 CFU, preferably 1x10 ^ CFU / g, determines a decrease in the Scorad index (a lower Scorad value indicates a better quality of life).

Inoltre, la somministrazione di detta composizione probiotica per un periodo compreso da 12 a 24 settimane, preferibilmente 16 settimane, Ã ̈ in grado di ridurre/bloccare la secrezione della citochina IL-4. Furthermore, the administration of said probiotic composition for a period ranging from 12 to 24 weeks, preferably 16 weeks, is able to reduce / block the secretion of the cytokine IL-4.

Parte sperimentale Experimental part

La Richiedente ha testato tutti e sei i ceppi sopra riportati . The Applicant tested all six of the above mentioned strains.

Un primo studio clinico à ̈ stato condotto per testare una composizione comprendente la coltura di Lactobacillus salivarius (LS01) DSM 22775 e la coltura di Bifidobacterium breve (BR03) DSM 16604. A first clinical study was conducted to test a composition comprising the culture of Lactobacillus salivarius (LS01) DSM 22775 and the culture of Bifidobacterium breve (BR03) DSM 16604.

Un gruppo di 40 pazienti (di sesso maschile e femminile di età compresa tra i 18 e i a 55 anni) con DA moderata/severa sono stati randomizzati (1:1) in due gruppi. A group of 40 patients (male and female aged 18 to 55 years) with moderate / severe AD were randomized (1: 1) into two groups.

La diagnosi di DA moderata/severa à ̈ stata valutata mediante l'utilizzo di un indice standardizzato di severità della DA (SCORAD index = SCORing Atopic Dermatitis). Tale indice à ̈ noto agli esperti del settore. The diagnosis of moderate / severe AD was assessed using a standardized index of AD severity (SCORAD index = SCORing Atopic Dermatitis). This index is known to experts in the field.

T0 rappresenta il tempo zero come punto di inizio del trattamento, mentre T16 rappresenta il periodo di 16 settimane di trattamento. Al T16 Ã ̈ stata eseguita una visita con Scorad e prelievo. T0 represents time zero as the starting point of treatment, while T16 represents the 16-week treatment period. A visit with Scorad and pickup was carried out at T16.

Il gruppo A Ã ̈ stato trattato con una composizione comprendente la coltura di Lactobacillus salivarius (LS01) DSM 22775 e la coltura di Bifidobacterium breve (BR03) DSM 16604, avente una concentrazione di 1x10® UFC (corrispondente a 0,01 g). Le due colture sono state miscelate con 1 g di amido di mais a dare una composizione finale in bustina di 1,01 g. Ai 20 pazienti del gruppo A sono state somministrate 2 bustine al giorno per 16 settimane. Group A was treated with a composition comprising the culture of Lactobacillus salivarius (LS01) DSM 22775 and the culture of Bifidobacterium breve (BR03) DSM 16604, having a concentration of 1x10® UFC (corresponding to 0.01 g). The two cultures were mixed with 1 g of corn starch to give a final sachet composition of 1.01 g. The 20 patients in group A were given 2 sachets per day for 16 weeks.

Il gruppo B Ã ̈ stato trattato con placebo rappresentato da 1 g di (solo) amido di mais. Ai 20 pazienti del gruppo B sono state somministrate 2 bustine di placebo al giorno per 16 settimane . Group B was treated with placebo represented by 1 g of (only) corn starch. The 20 patients in group B were given 2 placebo sachets per day for 16 weeks.

Sono state testate le seguenti citochine: Thl (IFN-γ e IL-12) e Th2 (IL-4, IL-5 e IL-10). The following cytokines were tested: Thl (IFN-γ and IL-12) and Th2 (IL-4, IL-5 and IL-10).

Tutti i dati dei 40 pazienti sono stati accuratamente raccolti e analizzati. All data from the 40 patients were carefully collected and analyzed.

La figura 1 mostra un istogramma relativo allo Scorad index a T0 e T16. Figure 1 shows a histogram relating to the Scorad index at T0 and T16.

I risultati ottenuti mostrano che l'assunzione, da parte dei 20 pazienti del gruppo A, della composizione probiotica comprendente la coltura di Lactobacillus salivarius (LS01) DSM 22775 e la coltura di Bifidobacterium breve (BR03) DSM 16604, ad una concentrazione di 1x10® UFC, determina una diminuzione dello Scorad nei pazienti affetti da DA (un valore di Scorad inferiore indica una qualità' della vita migliore) . The results obtained show that the assumption, by the 20 patients of group A, of the probiotic composition comprising the culture of Lactobacillus salivarius (LS01) DSM 22775 and the culture of Bifidobacterium breve (BR03) DSM 16604, at a concentration of 1x10® UFC, determines a decrease in Scorad in patients with AD (a lower Scorad value indicates a better quality of life).

Inoltre, la somministrazione di detta composizione probiotica per 16 settimane à ̈ in grado di bloccare la secrezione della citochina in esame IL-4, il cui valore medio à ̈ sovrapponibile a quello ottenuto al momento dell'arruolamento. Mentre, la somministrazione del placebo, invece, non à ̈ in grado di bloccare il rilascio della citochina IL- 4 tanto da risultare significativamente aumentata dopo 16 settimane di trattamento (evoluzione della malattia) . Furthermore, the administration of said probiotic composition for 16 weeks is able to block the secretion of the cytokine under examination IL-4, whose average value is comparable to that obtained at the time of enrollment. While, the administration of the placebo, on the other hand, is not able to block the release of the cytokine IL-4 so as to be significantly increased after 16 weeks of treatment (evolution of the disease).

Una serie di studi pre-clinici in vitro sono stati condotti su un gruppo di batteri comprendente, tra gli altri, anche la coltura di Lactobacillus salìvarius (LS01) DSM 22775 e la coltura di Bifidobacterìum breve (BR03) DSM 16604. A series of pre-clinical in vitro studies were conducted on a group of bacteria including, among others, the culture of Lactobacillus salìvarius (LS01) DSM 22775 and the culture of Bifidobacterìum breve (BR03) DSM 16604.

Studi pre-clinici in vitro di confronto tra le capacità immunomodulanti dei ceppi di batteri testati hanno dimostrato che la coltura di Lactobacillus salìvarius (LS01) DSM 22775 e la coltura di Bifidobacterìum breve (BR03) DSM 16604 mostrano una capacità superiore nell'indurre la produzione di citochine di tipo 1. In vitro pre-clinical studies comparing the immunomodulatory capacities of the tested bacterial strains have shown that the culture of Lactobacillus salìvarius (LS01) DSM 22775 and the culture of Bifidobacterì short (BR03) DSM 16604 show a superior capacity in 'induce the production of type 1 cytokines.

Anche le colture dei batteri Lactobacillus pentosus (LPS01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 e Lactobacillus acidophilus (LA02) DSM 21717, sono state testate . Cultures of Lactobacillus pentosus (LPS01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 and Lactobacillus acidophilus (LA02) DSM 21717, were tested.

La coltura del ceppo L. pentosus (LPS01) DSM 22775 ha dimostrato in vitro di indurre un profilo citochinico molto forte pro-Th1 . Culture of the L. pentosus (LPS01) DSM 22775 strain has been shown in vitro to induce a very strong pro-Th1 cytokine profile.

Inoltre, tutte le colture dei ceppi Lactobacillus pentosus (LPS 01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 e Lactobacillus acidophilus (LA02) DSM 21717 sono state testate per la loro capacità di induzione della sintesi di IL-12 da parte delle PBMCs in uno studio in vivo. La citochina IL-12 à ̈ di tipo Th1 e rappresenta un tassello chiave nel trattamento delle allergie e di altre patologie atopiche. In addition, all cultures of Lactobacillus pentosus (LPS 01) DSM 21980, Streptococcus thermophilus (FP4) DSM 18616, Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605 and Lactobacillus acidophilus (LA02) DSM 21717 were tested for their ability to induce IL-12 synthesis by PBMCs in an in vivo study. The cytokine IL-12 is of type Th1 and represents a key element in the treatment of allergies and other atopic diseases.

A titolo esemplificativo, vengono riportati i dati relativi a L. pentosus (LPS01) DSM 21980, testato su PBMCs: Th-1 (pg/ml) = 1,754; Th-2 (pg/ml) = 326; Thl/Th2 = 5,38. By way of example, the data relating to L. pentosus (LPS01) DSM 21980, tested on PBMCs, are reported: Th-1 (pg / ml) = 1.754; Th-2 (pg / ml) = 326; Thl / Th2 = 5.38.

Claims (10)

RIVENDICAZIONI 1. Una composizione comprendente almeno una coltura di batteri probiotici scelta dal gruppo comprendente le seguenti colture di batteri depositate presso il Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH,(DSMZ): Lactobacillus salivarius (LS01) DSM 22775, depositata il 23 .07.2009; Bifìdobacterium breve (BR03) DSM 16604, depositata il 20.072004; Lactobacillus pentosus (LPS01) DSM 21980, depositata il 14.11.2008 ; Streptococcus thermophilus (FP4) DSM 18616, depositata il 13.09.2006 ; Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605, depositata il 20.07.2004; e Lactobacillus acidophilus (LA02) DSM 21717, depositata il 06.08.2008, per uso nel trattamento preventivo e/o curativo della dermatite atopica. CLAIMS 1. A composition comprising at least one probiotic bacteria culture selected from the group comprising the following bacteria cultures deposited at Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, (DSMZ): Lactobacillus salivarius (LS01) DSM 22775, filed on 23.07.2009; Bifìdobacterium breve (BR03) DSM 16604, filed on 20.072004; Lactobacillus pentosus (LPS01) DSM 21980, filed on 14.11.2008; Streptococcus thermophilus (FP4) DSM 18616, filed on 13.09.2006; Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605, filed on 20.07.2004; And Lactobacillus acidophilus (LA02) DSM 21717, filed on 06.08.2008, for use in the preventive and / or curative treatment of atopic dermatitis. 2. La composizione per uso in accordo alla rivendicazione 1, in cui detta composizione comprende almeno una coltura di batteri probiotici scelta dal gruppo comprendente Lactobacillus salivarius (LS01) DSM 22775, Bifìdobacterium breve (BR03) DSM 16604 e Lactobacillus pentosus (LPS 01) DSM 21980. The composition for use according to claim 1, wherein said composition comprises at least one probiotic bacteria culture selected from the group comprising Lactobacillus salivarius (LS01) DSM 22775, Bifìdobacterium breve (BR03) DSM 16604 and Lactobacillus pentosus (LPS 01 ) DSM 21980. 3. La composizione per uso in accordo alla rivendicazione 2, in cui detta composizione à ̈ costituita da Lactobacillus salivarius (LS01) DSM 22775, Bifìdobacterium breve (BR03) DSM 16604 e L. pentosus (LPS01) DSM 21980. The composition for use according to claim 2, wherein said composition is constituted by Lactobacillus salivarius (LS01) DSM 22775, Bifìdobacterium breve (BR03) DSM 16604 and L. pentosus (LPS01) DSM 21980. 4. La composizione per uso in accordo a una qualsiasi delle rivendicazioni 1-3, in cui detta composizione à ̈ in forma solida per somministrazione orale. The composition for use according to any one of claims 1-3, wherein said composition is in solid form for oral administration. 5. La composizione per uso in accordo a una qualsiasi delle rivendicazioni 1-4, in cui dette colture di batteri probiotici sono presenti a una concentrazione compresa da 1x10^ a 1x10<11>UFC/g di composizione, preferibilmente da 1x10^ a 1x10<10>UFC/g di composizione. The composition for use according to any one of claims 1-4, wherein said cultures of probiotic bacteria are present at a concentration ranging from 1x10 ^ to 1x10 <11> CFU / g of composition, preferably from 1x10 ^ to 1x10 <10> CFU / g of composition. 6. La composizione per uso in accordo a una qualsiasi delle rivendicazioni 1-5, in cui detta composizione inoltre comprende fibre alimentari ad attività prebiotica scelte tra frutto-oligosaccaridi (FOS), inulina, gomma di guar parzialmente idrolizzata (PHGG). The composition for use according to any one of claims 1-5, wherein said composition further comprises dietary fibers with prebiotic activity selected from fructo-oligosaccharides (FOS), inulin, partially hydrolyzed guar gum (PHGG). 7. La composizione per uso in accordo a una qualsiasi delle rivendicazioni 1-5, in cui detta composizione à ̈ una composizione farmaceutica, dietetica, alimentare o nutraceutica . The composition for use according to any one of claims 1-5, wherein said composition is a pharmaceutical, dietary, food or nutraceutical composition. 8. Uso di almeno una coltura di batteri probiotici scelta dal gruppo comprendente le seguenti colture di batteri depositate presso il Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH,(DSMZ): Lactobacillus salivarius (LS01) DSM 22775, depositata il 23.07.2009; Bifidobacterium breve (BR03) DSM 16604, depositata il 20.072004; Lactobacillus pentosus (LPS01) DSM 21980, depositata il 14.11.2008 ; Streptococcus thermophilus (FP4) DSM 18616, depositata il 13.09.2006 ; Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605, depositata il 20.07.2004; e Lactobacìllus acidophilus (LA02) DSM 21717, depositata il 06.08.2008, per la preparazione di una composizione per il trattamento preventivo e/o curativo della dermatite atopica. 8. Use of at least one probiotic bacteria culture selected from the group comprising the following bacterial cultures deposited at Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, (DSMZ): Lactobacillus salivarius (LS01) DSM 22775, filed on 23.07.2009; Bifidobacterium brevis (BR03) DSM 16604, filed on 20.072004; Lactobacillus pentosus (LPS01) DSM 21980, filed on 14.11.2008; Streptococcus thermophilus (FP4) DSM 18616, filed on 13.09.2006; Lactobacillus casei ssp. rhamnosus (LR04) DSM 16605, filed on 20.07.2004; And Lactobacìllus acidophilus (LA02) DSM 21717, filed on 06.08.2008, for the preparation of a composition for the preventive and / or curative treatment of atopic dermatitis. 9. Uso secondo la rivendicazione 8, in cui detta composizione comprende la coltura di batteri probiotici in accordo alla rivendicazione 2 o 3. Use according to claim 8, wherein said composition comprises the culture of probiotic bacteria according to claim 2 or 3. 10. Uso secondo le rivendicazioni 8 o 9, in cui detta composizione à ̈ in accordo a una qualsiasi delle rivendicazioni da 4 a 7.Use according to claims 8 or 9, wherein said composition is according to any one of claims 4 to 7.
ITMI2010A000375A 2010-03-08 2010-03-08 COMPOSITION INCLUDING PROBIOTIC BACTERIA FOR THE TREATMENT OF PATHOLOGIES ASSOCIATED WITH THE ALTERATION OF THE IMMUNE SYSTEM. IT1398553B1 (en)

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JP2012556603A JP5931754B2 (en) 2010-03-08 2011-03-07 Compositions comprising probiotic bacteria for use in the treatment of immune diseases
PL13166218T PL2626076T3 (en) 2010-03-08 2011-03-07 Therapeutic uses of Lactobacillus salivarius LS01 DSM 22775
HUE13166218A HUE030888T2 (en) 2010-03-08 2011-03-07 Therapeutic uses of Lactobacillus salivarius LS01 DSM 22775
PCT/IB2011/000490 WO2011110918A1 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
DK11717732.9T DK2544698T3 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in treatment of immune disorders
ES13166218.1T ES2603629T3 (en) 2010-03-08 2011-03-07 Therapeutic uses of Lactobacillus salivarius LS01 DSM 22775
CN201510082517.4A CN104800247A (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
RU2012140052/15A RU2605293C2 (en) 2010-03-08 2011-03-07 Composition, containing probiotic bacteria for use in treating immune disorders
HUE11717732A HUE029245T2 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
PT131662181T PT2626076T (en) 2010-03-08 2011-03-07 Therapeutic uses of lactobacillus salivarius ls01 dsm 22775
US13/583,477 US8734783B2 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
RU2016129186A RU2712751C9 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in treating immune disorders
AU2011225798A AU2011225798B2 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
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BR112012022755-6A BR112012022755B1 (en) 2010-03-08 2011-03-07 composition with probiotic bacteria for use in the treatment of immunological disorders
EP13166218.1A EP2626076B1 (en) 2010-03-08 2011-03-07 Therapeutic uses of Lactobacillus salivarius LS01 DSM 22775
KR1020127026327A KR101872946B1 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
PL11717732T PL2544698T3 (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
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CN201180019385.0A CN103037876B (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
CA2792343A CA2792343C (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
DK13166218.1T DK2626076T3 (en) 2010-03-08 2011-03-07 Therapeutic uses of Lactobacillus salivarius DSM 22775 LS01
PT117177329T PT2544698T (en) 2010-03-08 2011-03-07 Composition comprising probiotic bacteria for use in the treatment of immune disorders
UAA201211024A UA111715C2 (en) 2010-03-08 2011-07-03 A COMPOSITION CONTAINING PROBiotIC BACTERIA FOR IMPLEMENTATION IN THE TREATMENT OF IMMUNE DISORDERS
ZA2012/07377A ZA201207377B (en) 2010-03-08 2012-10-02 Composition comprising probiotic bacteria for use in the treatment of immune disorders
US14/286,308 US9498503B2 (en) 2010-03-08 2014-05-23 Composition comprising probiotic bacteria for use in the treatment of immune disorders
ZA2014/09369A ZA201409369B (en) 2010-03-08 2014-12-18 Composition comprising probiotic bacteria for the treatment of pathologies associated with alterations of the immune system
JP2016029244A JP6182628B2 (en) 2010-03-08 2016-02-18 Compositions comprising probiotic bacteria for use in the treatment of immune diseases
US15/294,464 US9931363B2 (en) 2010-03-08 2016-10-14 Composition comprising probiotic bacteria for use in the treatment of immune disorders

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